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This paper explores the challenges and opportunities of scholarly publishing in sub-Saharan Africa in the twenty-first century. The paper also proposes ways of capitalizing on the vast opportunities of enhancing knowledge production and dissemination in sub-Saharan Africa through scholarly publishing in the twenty-first century. An analysis of publication records of sub-Saharan Africa between 1997 and 2007 in the Thompson Scientific was conducted. There are many challenges confronting scholarly publishing in sub-Saharan Africa. The challenges include technological, socio-political, economic and environmental. The 21st century brings with it opportunities that may enhance sub-Saharan Africa's visibility of scholarly publishing.